The invention relates to vaccine compositions, methods of making vaccines, and methods of vaccine administration.
Many antigens, particularly those associated with a pathogen's capsule layer stimulate little or no immune response and complicate efforts to create effective vaccines against those antigens. Capsules are surface components of microbes that are typically composed of polymers of organic compounds such as carbohydrates, amino acids, or alcohols. Capsules are quite diverse chemically. The monomeric units that make up capsules (e.g., carbohydrates) can be linked together in various molecular configurations and can be further substituted with phosphate, nitrogen, sulfate, and other chemical modifications. These chemical variations allow capsules to present numerous antigenic targets on the microbial surface thus allowing escape from the host immune system directed at these targets. Capsules can also be virulence factors which prevent microbes from being phagocytosed and killed by host macrophages and polymorphonuclear leukocytes. Antibodies against capsules provide a potent defense against encapsulated organisms by fixing complement to the microbial surface, which can result in their lysis or their opsonization, uptake, and killing by phagocytic host immune cells. The most potent antibodies against capsules are IgG antibodies. Capsules that fail to induce significant levels of IgG are called T-independent antigens. Covalent coupling of a protein to capsule renders them “T-dependent” and such antigens can elicit an IgG response.
There is a need for safe, synthetically accessible, cost-effective vaccines directed to capsule and other T-independent antigens that do not evoke strong immune responses or IgG antibody. Such vaccines are needed to protect against various infectious diseases such as infection by anthrax, pneumococcus, influenzae Type B, meningococcus, and streptococcus.